Spinning Disk Confocal Microscope system. Eleven Major Users and 4 Minor Users, each with ongoing NIH grant support and extensive technical experience and expertise in fluorescence microscopy, request funds to purchase a Marianas SDC spinning disk microscope from Intelligent Imaging Innovations (3I). Two microscopes (one inverted and one upright) will share a Yokogawa CSU-X1 micro-lens spinning disk unit and 4 excitation laser lines (405, 488, 561, and 640 nm). Other accessories are described below. Significant institutional funds ($100,000) will assist in purchase of the instrument, which will be housed in and maintained by the campus-wide Light Microscopy Facility, making it broadly available to researchers and insuring successful long-term maintenance and security. All 15 research projects involve live cell imaging. Extensive pilot data have demonstrated the unique capabilities of the instrument, such as greatly reduced photo-damage and photo-bleaching, rapid acquisition of multiple image stacks, and ability to achieve diffraction-limited resolution (inverted microscope) and accommodate thick tissue imaging and electrophysiology (upright microscope). None of the proposed research projects can be accomplished with any equipment available to us on our campus or at neighboring institutions.